Differential effect of hypophysectomy and growth hormone treatment on hepatic glucuronosyltransferases in male rats: evidence for an action at a pretranslational level for isoforms glucuronidating bilirubin.

• Main Authors: Guéraud, Françoise, Masmoudi, T, Goudonnet, H, Paris, Alain
• Other Authors: Xénobiotiques, Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), UFR PHARMACIE, Université de Bourgogne (UB)
• Format: Article in Journal/Newspaper
• Language: English
• Published: HAL CCSD 1997
• Subjects: Rat; Biochimie; Objet d'étude : rattus rattus; foie Composé chimique; Facteur du milieu : transférase; hormone de croissance Dispositif technique et méthode d'étude : médicament; hypophysectomie Phénomène; processus et fonction : pulsatilité; [SDV]Life Sciences [q-bio]; Rattus rattus
• Online Access: https://hal.inrae.fr/hal-02698225

International audience The influence of growth hormone (GH) on 4-nitrophenol, bilirubin, testosterone, androsterone and estrone glucuronidation activities was studied in fully activated male rat hepatic microsomes. Sham-operated and hypophysectomized animals were injected with two different dosages of GH, mimicking either the male or female GH secretion pattern. Half the animals received thyroxine and cortisol in concentrations chosen to compensate for the lack of thyroid hormones and glucocorticoids in hypophysectomized rats. GH induced a decrease in several glucuronidation activities: bilirubin glucuronidation in both sham-operated and cortisol/ thyroxine-treated hypophysectomized rats in a dose-dependent manner, testosterone glucuronidation in hypophysectomized animals, and androsterone and estrone glucuronidation in cortisol/thyroxin-treated hypophysectomized rats. 4-nitrophenol glucuronidation was not affected by GH treatment. A hypothetical "feminizing" effect of GH (due to an almost continuous secretion) could not be invoked to explain these results, contrary to what has been observed elsewhere for other hepatic enzyme activities. Hypophysectomy altered all the activities tested, with bilirubin the most modified (a 200% enhancement). Restoration of control values was achieved in hypophysectomized animals with cortisol/thyroxine replacement together with a low dosage of GH (mimicking a male GH secretion pattern), except for androsterone glucuronidation activity where both GH and cortisol/thyroxine treatments reinforced the decreasing effect of hypophysectomy. Variations in protein amounts were correlated to variations in bilirubin, testosterone and androsterone conjugation activities induced by hypophysectomy and GH treatment. Reverse transcription-polymerase chain reaction (RT-PCR) mRNA analysis of bilirubin cluster isoforms or uridine diphosphate glucuronosyltransferase 1B1 (UGT1B1), UGT1B2 and UGT1B5 showed that GH controlled the different isoforms involved in bilirubin glucuronidation differentially ...